Raw vegetable food containing high cyclo (his-pro) improved insulin sensitivity and body weight control
VA Greater Los Angeles Healthcare System, Los Ángeles, California, United StatesMetabolism (Impact Factor: 3.89). 12/2005; 54(11):1480-9. DOI: 10.1016/j.metabol.2005.05.014
Cyclo (his-pro), controlled-energy diet, soy protein hydrolysate (SPH), and raw vegetable food (RVF) are known to improve insulin sensitivity and body weight (BW) control. Enhancement of high cyclo (his-pro) content in SPH (HCS) was performed by refluxing SPH with 1 N KH(2)CO(3) dissolved in 70% ethanol for 2 weeks at room temperature. Using this material, we examined the effects of HCS plus RVF on glucose metabolism and BW control in genetically diabetic Goto-Kakizaki (G-K) and insulin-resistant aged overweight Sprague-Dawley (S-D) rats. Thirty 7-week-old G-K rats and 18 16- to 18-month-old S-D rats were divided into 3 groups and treated with normal chow (NC), RVF diet, or HCS diet for 8 weeks. Raw vegetable food diet was made of 1:3 RVF and 2:3 NC; HCS diet was made of 1:27 portion HCS, 8:27 RVF, and 2:3 NC. Oral glucose tolerance significantly improved in both RVF- (P<.01) and HCS-treated (P<.001) G-K rats and worsened in NC-fed rats compared with the baseline values. Similarly, oral glucose tolerance also improved in aged overweight S-D rats when treated with RVF (P<.05) and with HCS (P<.01), compared with the baseline values. Although HCS diet treatment very significantly lowered fed plasma insulin levels compared with NC diet treatment in G-K rats (P<.01), RVF diet treatment alone did not decrease plasma insulin levels. In contrast, there was no change of insulin levels in overweight aged S-D rats after either RVF or HCS diet treatment. Postfeeding glucose levels in G-K rats fed RVF or HCS significantly fell, compared with the rats fed NC (P<.05). Interestingly, fasting blood glucose levels in RVF- or HCS-fed rats were very significantly lower than in NC-fed rats (P<.001). There was no change of blood glucose levels in S-D rats due to treatments with different diet. In G-K rats, food intake did not decrease during the first 3 weeks but fell very significantly from the fifth to eighth weeks with RVF (P<.01) and HCS (P<.001) treatments in G-K rats. However, food intake reduction in aged S-D rats was shown only for the HCS-treated rat group (P<.05). Water intake slightly decreased in G-K rats with either RVF or HCS treatment (P<.05) but very significantly decreased in S-D rats with HCS treatment (P<.01). Body weight gain in young G-K rats and BW in aged S-D rats significantly decreased only when rats were treated with HCS diet (P<.05). These data suggest that regular consumption of HCS diet helps to control blood glucose metabolism in diabetic G-K rats and BW control in aged obese S-D rats.
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ABSTRACT: The effects of Cyclo (His-Pro) (CHP), a cyclic dipeptide structurally related to thyrotropin-releasing hormone (TRH), on glucose metabolism, blood insulin level, lipid profile, and the viability of pancreatic cells were investigated in streptozotocin (STZ)-induced diabetic rats. The rats (Sprague-Dawley) with a blood glucose level above 300 mg/dL after induction with STZ (50 mg/kg of body weight) were considered to be diabetic and used for the treatment with CHP (4 mg/day/kg of body weight). The blood glucose level in the CHP-fed rats was reduced remarkably by approximately 56% as compared to the untreated diabetic group at 21 days of feeding. In an oral glucose tolerance test, blood glucose levels were restored to baseline at 120 min after CHP treatment, although the levels increased significantly after 30 min. Plasma insulin levels in the CHP-treated group were also enhanced by 2-fold compared to the untreated group. Triglyceride and total cholesterol levels in CHP-treated rats almost returned to normal levels. Moreover, histological examination showed that CHP treatment restored impaired β-cells in the pancreas up to two-thirds of the normal level. The transcriptional level of C-reactive protein (CRP), used mainly as a marker of inflammation, was also restored mimicking normal level in the CHP-treated-group, suggesting that the β-cells destroyed by STZ were, at least in part, recovered. Accordingly, CHP was concluded to have an excellent hypoglycemic effect by lowering average plasma glucose levels, increasing insulin secretion, and restoring the viability of pancreatic β-cells in diabetic rats. We suggest that CHP might be a potential candidate to control Type I diabetes mellitus.
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ABSTRACT: This study examined the possible effects of lycopene at physiological dosage and body fat mass on the humoral immune response in patients with type 2 diabetes mellitus (T2DM). A total of 35 patients with Typ2 diabetes mellitus from both sexes aged 54+/-9 yrs from the Iranian Diabetes Society were introduced into a double blind placebo controlled clinical trial conducted for 2 months. After a 2-week lycopene free diet washout period, patients were allocated to either lycopene supplementation group (10mg/d) (n=16) or placebo age- and sex matched group (n=19) for 8 weeks. Patients were instructed to keep their diets and physical activities as unchanged as possible. Lycopene supplements increased serum lycopene levels (p<0.001). While intake of dietary energy and nutrients did not change in either groups, the ratio of total antioxidant capacity to malondialdehyde increased significantly in the lycopene group (p=0.007). There was an inverse correlation between serum levels of lycopene and those of IgG (r= -0.338, p=0.008). On the contrary, changes of serum levels of lycopene directly correlated with those of IgM (r=0.466, p=0.005). Interestingly, changes of the amount of fat mass correlated directly with those of serum IgG (r=0.415, p=0.044) but inversely with of serum IgM (r= -0.469, p=0.021). While truncal fat might promote adaptive humoral immunity, lycopene probably by inhibiting MDA-LDL formation might attenuate T cell dependent adaptive (pro-atherogenic) humoral immune response. These findings may have preventive implications in long term diabetic complications, notably atherogenesis.
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ABSTRACT: This study was undertaken to evaluate the antioxidant effects of lycopene in physiological doses and its possible effects on the immune response in patients with Type 2 diabetes mellitus (T2DM). A total of 35 patients with T2DM of both sexes aged 54+/-9 yr were enrolled in a double-blind placebo-controlled clinical trial conducted for 2 months. After a 2-week lycopene-free diet washout period, patients were allocated to either lycopene supplementation group (10 mg/day) (no.=16) or placebo group (no.=19), which were age- and sex matched. Patients were instructed to keep their diet and physical activity as unchanged as possible. While dietary intake of energy and body weight did not change, the ratio of serum total antioxidant capacity (TAC) to malondialdehyde (MDA) increased significantly in the lycopene group compared to the placebo group (p=0.007). Though a statistically significant increase in serum concentrations of lycopene (p<0.001) was not accompanied by enhanced delayed-type hypersensitivity response, a significant negative correlation was found between serum levels of lycopene and immunoglobulin (Ig)G (r=-0.338, p=0.008). Interestingly, variations of serum levels of lycopene directly correlated with those of IgM (r=0.466, p=0.005). There was an insignificant decrement in serum anti-oxidized LDL IgG levels in the lycopene group. Lycopene, probably by increasing TAC and inhibiting MDA-LDL formation, may attenuate T cell-dependent adaptive (pro-atherogenic) immune response. Meanwhile, with enhancement of innate immunity and hence prevention of ox-LDL uptake by macrophage and foam cell formation, lycopene may be effective in prevention of long-term diabetic complications, notably cardiovascular disease.
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